title: Influence of hepatic dysfunction on the pharmacokinetics and safety of fimasartan.
abstract: This study was designed to assess the pharmacokinetics (PK) and safety of fimasartan, an angiotensin II type 1 receptor blocker, in hepatic impairment patients as compared with healthy subjects. An open-label, single-dose, parallel study was conducted in 6 healthy male volunteers and 12 subjects with hepatic impairment. Healthy subjects were matched with hepatic dysfunction patients on the basis of age, gender, and body weight. After a single 120-mg oral administration of fimasartan, PK parameters and safety were analyzed between the hepatic dysfunction groups and healthy group. Compared with the healthy subjects, the geometric mean ratio and 90% confidence intervals for the maximum plasma concentration and the mean area under the plasma concentration-time curve from 0 to infinity (AUC)inf were 0.77 (0.24-2.47) and 1.11 (0.50-2.46), respectively, for the mild hepatic impairment and 6.55 (3.56-12.03) and 5.17 (4.19-6.37), respectively, for moderate hepatic impairment. However, there was no significant difference in time to peak plasma concentration (t(max)) and elimination half-life, and there were no serious or severe adverse events in all subjects. Subjects with mild hepatic impairment exhibited similar bioavailability compared with healthy subjects, whereas subjects with moderate hepatic impairment seemed to exhibit a higher level of systemic exposure to fimasartan than healthy subjects. In addition, all subjects were tolerable with fimasartan.
authors.affiliation: *Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea; †Clinical Trial Center, Kyungpook National University Hospital, Daegu, Korea; ‡Department of Biomedical Science, Kyungpook National University Graduate School, Daegu, Korea; §Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; and ¶Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Choon Ok
authors.initials: CO
authors.lastname: Kim
authors.forename: Hae Wan
authors.initials: HW
authors.lastname: Lee
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Oh
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Seong
authors.forename: Do Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Joomi
authors.initials: J
authors.lastname: Lee
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Cho
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Park
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D048550:Hepatic Insufficiency / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D056910:Republic of Korea; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D011743:Pyrimidines; D013777:Tetrazoles; C558933:fimasartan